The enzymatic activity of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase is enhanced by NPM-ALK: new insights in ALK-mediated pathogenesis and the treatment of ALCL
| العنوان: | The enzymatic activity of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase is enhanced by NPM-ALK: new insights in ALK-mediated pathogenesis and the treatment of ALCL |
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| المؤلفون: | Ludovica Riera, Michael J. Comb, Claudia Voena, Giorgio Inghirami, Francesco Boccalatte, Amalia Bosia, Ole N. Jensen, Roberto D. Polakiewicz, John Rush, Julie Nardone, Valerie Goss, Bruce Ruggeri, Mangeng Cheng, Kimberly Lee, Roberto Chiarle, Chiara Riganti, Lucia D'Amico |
| المصدر: | Boccalatte, F E, Voena, C, Riganti, C, Bosia, A, D'Amico, L, Riera, L, Cheng, M, Ruggeri, B, Jensen, O N, Goss, V L, Lee, K, Nardone, J, Rush, J, Polakiewicz, R D, Comb, M J, Chiarle, R & Inghirami, G 2009, ' The enzymatic activity of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) is enhanced by NPM-ALK : new insights in ALK-mediated pathogenesis and the treatment of ALCL ', Blood, vol. 8, no. 3, pp. 2776-2790 . https://doi.org/10.1182/blood-2008-06-161018Test |
| بيانات النشر: | American Society of Hematology, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Hydroxymethyl and Formyl Transferases, Antimetabolites, Antineoplastic, Indazoles, Transcription, Genetic, Molecular Sequence Data, Immunology, Carbazoles, Biology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Multienzyme Complexes, RNA interference, Cell Line, Tumor, hemic and lymphatic diseases, Protein Interaction Mapping, medicine, Humans, Anaplastic lymphoma kinase, Amino Acid Sequence, Phosphorylation, Phosphotyrosine, Protein Kinase Inhibitors, Anaplastic large-cell lymphoma, 030304 developmental biology, 0303 health sciences, Kinase, Gene Expression Profiling, Phenylurea Compounds, Microfilament Proteins, IMP cyclohydrolase, Cell Biology, Hematology, Protein-Tyrosine Kinases, Phosphoproteins, medicine.disease, Molecular biology, Fusion protein, Neoplasm Proteins, Methotrexate, Drug Resistance, Neoplasm, Nucleotide Deaminases, 030220 oncology & carcinogenesis, Cancer research, Lymphoma, Large-Cell, Anaplastic, Cell Adhesion Molecules, Protein Processing, Post-Translational, Tyrosine kinase |
| الوصف: | Anaplastic large cell lymphoma represents a subset of neoplasms caused by translocations that juxtapose the anaplastic lymphoma kinase (ALK) to dimerization partners. The constitutive activation of ALK fusion proteins leads to cellular transformation through a complex signaling network. To elucidate the ALK pathways sustaining lymphomagenesis and tumor maintenance, we analyzed the tyrosine-kinase protein profiles of ALK-positive cell lines using 2 complementary proteomic-based approaches, taking advantage of a specific ALK RNA interference (RNAi) or cell-permeable inhibitors. A well-defined set of ALK-associated tyrosine phosphopeptides, including metabolic enzymes, kinases, ribosomal and cytoskeletal proteins, was identified. Validation studies confirmed that vasodilator-stimulated phosphoprotein and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC) associated with nucleophosmin (NPM)–ALK, and their phosphorylation required ALK activity. ATIC phosphorylation was documented in cell lines and primary tumors carrying ALK proteins and other tyrosine kinases, including TPR-Met and wild type c-Met. Functional analyses revealed that ALK-mediated ATIC phosphorylation enhanced its enzymatic activity, dampening the methotrexate-mediated transformylase activity inhibition. These findings demonstrate that proteomic approaches in well-controlled experimental settings allow the definition of informative proteomic profiles and the discovery of novel ALK downstream players that contribute to the maintenance of the neoplastic phenotype. Prediction of tumor responses to methotrexate may justify specific molecular-based chemotherapy. |
| تدمد: | 1528-0020 0006-4971 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe653880cf5274903cc11ecefb5fa79fTest https://doi.org/10.1182/blood-2008-06-161018Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fe653880cf5274903cc11ecefb5fa79f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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